The Role Of Connexin36in Epilepsy

Objective:Epilepsy is a kind of chronic cerebral disease characterized by recpetitive paroxysmaland transient central nervous system(CNS) dysfunction caused by abnormal discharge ofneurons Gap junctions was considered to play an important role in the process ofepilepsy..In this study, we used injection of PTZ to set up acute epilepsy model, on this basis,CBX were added ot Examine the role of gap junction in the phatogenesis of epilepsy bytesting the Expression of Cx36and Caspase-3、Bcl-2、Bax in the brain of rats.Methods:we used injection of PTZ to set up acute epilepsy model, rats were randomly dividedinto3groups: contral group,.PTZ-induced seizure model group,CBX interfering group. Theexperiment observed the changes of behavior and EEG in seizure rats, investigations of theexpression of Cx36and Caspase-3、Bcl-2、Bax in hippocampus by the methods of HEstaining, immunohistochemical staining, Western blot, to further understanding of the role ofgap junctions in the mechanisms of epileptogenesis.Results:1. EEG of PTZ-induced seizure model rats is abnormal, it included polyspikedischarges and spike-wave complexes.2. The immunohistochemical staining showed that Cx36expressed in rat cortex andhippocampus, cytoplasmic immunoreactivity is distributed mainly in the neurons. Theexpression of Cx36is obviously in CA1and CA3region of hippocampus. The expression ofCx36protein is increased from2h, and continued to24h in PTZ and CBX groups. Comparedwith the normal group at the same time, Cx36increased significantly in CA1and CA3area in the CBX group and PTZ group. CBX group compared with PTZ group, there is nodifference for the number of Cx36positive cells significantly.3. The Western blot results show that Cx36protein expression were increased from2hand continued to24h in PTZ and CBX groups, and consistent with immunohistochemicalstaining results. The expression of Caspase-3and Bax increased obviously in PTZ group andCBX group after24h. CBX group compared with PTZ group, the expression of Caspase-3and Bax were decreased. The expression of Bcl-2decreased obviously in PTZ group andCBX group after24h. CBX group compared with PTZ group, the expression of Bcl-2wasincreased.Conclusions:Cx36expression was significantly increased in PTZ induced epilepsy rats brain, theexpression of Cx36had no effect in CBX group, but the expression of Caspase-3and Baxprotein decreased obviously in the CBX group than PTZ group, the expression of Bcl-2protein increased obviously in the CBX group than PTZ group. The results suggest thatinhibition of gap junctions will affect the neurons abnormal synchronized firing activities,and reduce neuronal cell apoptosis caused by seizure. It also suggested that over expressionof Cx36in the process of seizures may increase the gap junction numbers between neurons,promote neuronal abnormal synchronized firing activity, and induced apoptosis of neuralcells.